dbSNP rs778121953: ONECUT2:p.Gly34Arg (chr18-57435816-G-A) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4BS2

The NM_004852.3(ONECUT2):c.100G>A(p.Gly34Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000508 in 984,476 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G34W) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000051 ( 0 hom. )

Consequence

ONECUT2
NM_004852.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.11

Publications

1 publications found

Variant links:

Genes affected

ONECUT2 (HGNC:8139): (one cut homeobox 2) This gene encodes a member of the onecut family of transcription factors, which are characterized by a cut domain and an atypical homeodomain. The protein binds to specific DNA sequences and stimulates expression of target genes, including genes involved in melanocyte and hepatocyte differentiation. [provided by RefSeq, Jul 2008]

ONECUT2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2896188).

BS2

High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ONECUT2	NM_004852.3 link	c.100G>A	p.Gly34Arg	missense_variant	Exon 1 of 2	ENST00000491143.3	NP_004843.2	O95948

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ONECUT2	ENST00000491143.3 link	c.100G>A	p.Gly34Arg	missense_variant	Exon 1 of 2	1	NM_004852.3	ENSP00000419185.2		O95948

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000291

AC:

AN:

137254

AF XY:

0.0000504

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000595

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000508

AC:

AN:

984476

Hom.:

Cov.:

AF XY:

0.00000629

AC XY:

AN XY:

476944

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

18906

American (AMR)

AF:

0.00

AC:

AN:

15114

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

10572

East Asian (EAS)

AF:

0.00

AC:

AN:

8562

South Asian (SAS)

AF:

0.00

AC:

AN:

34664

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21772

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2308

European-Non Finnish (NFE)

AF:

0.00000595

AC:

AN:

839678

Other (OTH)

AF:

0.00

AC:

AN:

32900

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.435

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000263

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.60

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.21

Eigen

Benign

0.14

Eigen_PC

Benign

0.090

FATHMM_MKL

Benign

0.76

LIST_S2

Benign

0.50

M_CAP

Pathogenic

0.54

MetaRNN

Benign

0.29

MetaSVM

Benign

-0.80

MutationAssessor

Uncertain

2.3

PhyloP100

5.1

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

0.080

REVEL

Uncertain

0.36

Sift

Benign

0.14

Sift4G

Uncertain

0.056

Polyphen

1.0

Vest4

0.35

MutPred

0.30

Loss of glycosylation at T31 (P = 0.066);

MVP

0.48

MPC

1.9

ClinPred

0.59

GERP RS

1.9

PromoterAI

0.046

Neutral

(source)

Varity_R

0.26

gMVP

0.37

Mutation Taster

=77/23

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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rs778121953

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over